April 28,2008

Senator Grassley asks FDA about techniques for screening the pharmaceutical supply chain

April 28, 2008

Via Electronic Transmission

The Honorable Andrew C. von Eschenbach, M.D.
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Commissioner von Eschenbach:

As Ranking Member of the Committee on Finance (Committee), I have aresponsibility to the more than 80 million Americans who receive health care coverageunder the Medicare and Medicaid programs to oversee the proper administration of theseprograms and ensure that taxpayer and beneficiary dollars are appropriately spent on safeand effective drugs and devices.

An increasing amount of the drugs and active pharmaceutical ingredients (API)Americans use are being manufactured in foreign countries. Yet, as reported by theGovernment Accountability Office (GAO) in November 2007, the Food and DrugAdministration (FDA or Agency) does not know how many foreign establishments aresubject to inspection and the Agency conducts relatively few inspections each year. As Iam sure you will agree, it is critical that sufficient standards be in place to ensureaccountability and the quality of the drug products we import into this country. To dootherwise can have devastating results, as the heparin situation so aptly demonstrates.This blood-thinning drug is a life-saving and life-sustaining medication. It is myunderstanding that there is only one company that has developed a traceable distributionsystem that provided sufficient assurances to the FDA so that the company can continueproviding heparin to the American public and many throughout the world. It is with thisin mind that I am writing to you today.

The FDA’s investigation of the contamination of the U.S. heparin supplyhighlighted significant weaknesses in oversight of the production and supply chain.While one manufacturer, Baxter, conducted audits and inspections of its heparin APIsupplier, Changzhou SPL, there were no mechanisms ensuring that the upstreamproviders—the consolidators, the crude heparin processors, and the slaughterhouses—were providing a quality product to Changzhou SPL. Prior to the recall of its heparinproducts, Baxter manufactured about 50 percent of the heparin sodium used in the UnitedStates.

Last week, my staff was briefed on a traceable distribution system, which tracksthe production of its heparin sodium from the pig through manufacture of the finalproduct. The company using this system has its own facility in China to purify the crudeheparin and informed my staff that it had already been testing its heparin using one of thetwo methods that FDA subsequently required of all heparin manufacturers to screen forthe contaminant in their API. It is my understanding that this company developed itstraceable distribution system in 2003 to ensure that the extraction and purification ofcrude heparin was conducted under strict controls. In 2005 this same company obtainedthe FDA’s approval to use this system for its heparin production. It appears that becauseof the system this company has in place, it was able to avoid contamination of its heparinAPI. As I understand it, no other heparin manufacturer employs a similar trackingsystem.

Accordingly, please respond to the following questions by no later than May 19,2008:

1. In your opinion, if other manufacturers had a traceable distribution system like theone described in this letter, would the contamination of our heparin supply beenavoided or at least significantly limited? Could this system reasonably be put inplace by other manufacturers? If not why not?

2. During last week’s telebriefing, the FDA stated that the heparin eventsdemonstrated a need for more well-developed testing and screening methods aswell as an enhanced scrutiny of the supply chain. What steps is FDA taking toensure greater oversight of the supply chain?

3. I understand that the FDA is working with U.S. Pharmacopeia to revise andupdate the current testing methods for detecting contaminants in heparin. Has theFDA sought input from all stakeholders or experts on developing methods andstandards that will ensure the quality of our heparin supply? Please identify anyother stakeholders or experts being consulted.

4. Is it your understanding that, prior to this year’s contamination, there was onlyone heparin manufacturer employing a system to track and trace the manufactureof heparin at all stages of production?

Thank you for your attention to this important matter. If you have any questions,please do not hesitate to contact Emilia DiSanto or Angela Choy at (202) 224-4515. Allformal correspondence should be sent electronically in PDF format toBrian_Downey@finance-rep.senate.gov or via facsimile to (202) 228-2131.


Charles E. Grassley
Ranking Member